David A. Tanen

Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop

BackgroundEnvenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists.MethodsA geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm.ResultsA unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy.ConclusionsClinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.

Hydroxocobalamin and sodium thiosulfate versus sodium nitrite and sodium thiosulfate in the treatment of acute cyanide toxicity in a swine (Sus scrofa) model.

STUDY OBJECTIVE Cyanide can cause severe hypotension with acute toxicity. To our knowledge, no study has directly compared hydroxocobalamin and sodium nitrite with sodium thiosulfate in an acute cyanide toxicity model. Our objective is to compare the return to baseline of mean arterial blood pressure between 2 groups of swine with acute cyanide toxicity and treated with hydroxocobalamin with sodium thiosulfate or sodium nitrite with sodium thiosulfate. METHODS Twenty-four swine were intubated, anesthetized, and instrumented (continuous arterial and cardiac output monitoring) and then intoxicated with a continuous cyanide infusion until severe hypotension. The animals were divided into 2 arms of 12 each and then randomly assigned to intravenous hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) or sodium nitrite (10 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 40 minutes after start of antidotal infusion. Twenty animals were needed for 80% power to detect a significant difference in outcomes (alpha 0.05). Repeated measures of analysis of covariance and post hoc t test were used for determining significance. RESULTS Baseline mean weights, time to hypotension (31 minutes 3 seconds versus 28 minutes 6 seconds), and cyanide dose at hypotension (5.6 versus 5.9 mg/kg) were similar. One animal in the hydroxocobalamin group and 2 animals in the sodium nitrite group died during antidote infusion and were excluded from analysis. Hydroxocobalamin resulted in a faster return to baseline mean arterial pressure, with improvement beginning at 5 minutes and lasting through the conclusion of the study (P<.05). No statistically significant difference was detected between groups for cardiac output, pulse rate, systemic vascular resistance, or mortality at 40 minutes post intoxication. Mean cyanide blood levels (4.03 versus 4.05 microg/mL) and lactate levels (peak 7.9 versus 8.1 mmol/L) at hypotension were similar. Lactate levels (5.1 versus 4.48 mmol/L), pH (7.40 versus 7.37), and base excess (-0.75 versus 1.27) at 40 minutes were also similar. CONCLUSION Hydroxocobalamin with sodium thiosulfate led to a faster return to baseline mean arterial pressure compared with sodium nitrite with sodium thiosulfate; however, there was no difference between the antidote combinations in mortality, serum acidosis, or serum lactate.

Serious Bacterial Infections in Febrile Infants in the Post―Pneumococcal Conjugate Vaccine Era

OBJECTIVES The objective was to identify the epidemiology of serious bacterial infections (SBI) and the current utility of obtaining routine complete blood counts (CBC) and blood cultures to stratify infants at risk of SBI, in the study population of febrile infants in the post-heptavalent pneumococcal conjugate vaccine (PCV7) era. METHODS A cohort study with nested case-controls was undertaken at a tertiary care military hospital emergency department (ED) from December 2002 through December 2003. Irrespective of clinical findings at the initial encounter, patients were included if they were under 3 months of age and had a home or ED temperature of >or=100.4 degrees F or if they were between 3 and 24 months of age with a temperature of >or=102.3 degrees F. Data abstracted included age, temperature, peripheral white blood cell (WBC) count, and discharge diagnosis. Culture (blood, urine, and cerebrospinal fluid [CSF]) and chest radiograph (CXR) results were obtained through review of the electronic hospital archives. SBI was defined as pneumonia, urinary tract infection (UTI), meningitis, or bacteremia. RESULTS A total of 985 children aged 0 to 24 months were enrolled. Fifty-five percent were male, the median age was 12 months (interquartile range = 8-17 months), and 79% had received at least one PCV7. A total of 132 cases of SBI were identified in 129 infants (13.1%): 82 pneumonias, 45 UTI, five bacteremias, and no cases of bacterial meningitis. The frequency of bacteremia was 0.7%. No statistical difference was detected in the WBC count between the SBI and non-SBI groups (13.8 +/- 5.8 and 11.7 +/- 5.6, respectively; p = 0.055). No readily available WBC cutoff on the receiver operating characteristic (ROC) curve proved to be an accurate predictor of SBI. No statistical difference was detected in mean temperature between the SBI and non-SBI groups (103.3 +/- 1.2 and 103.2 +/- 1.2 degrees F, respectively; p = 0.26), nor was there a difference noted when groups were broken down by age or height of fever. CONCLUSIONS The WBC count and height of fever were not found to be accurate predictors of SBI in infants age 3 to 24 months. UTI and pneumonias made up the vast majority of SBI in this population of infants. The overall bacteremia frequency was well below 1%. This calls into question the continued utility of obtaining routine complete cell counts and blood cultures in the febrile infant in the post-PCV7 era.

Failure of intravenous N-Acetylcysteine to reduce methemoglobin produced by sodium nitrite in human volunteers: A randomized controlled trial

STUDY OBJECTIVE To determine whether intravenous N -acetylcysteine (NAC) produces a clinically significant decline in sodium nitrite-induced methemoglobinemia in human volunteers. METHODS We conducted a randomized, control crossover trial with each subject serving as his own control. Methemoglobinemia was induced with intravenous sodium nitrite (4 mg/kg) administered over 10 minutes starting at time 0. At time 30 minutes, subjects were randomly assigned to treatment with intravenous NAC for 100 minutes (150 mg/kg over 1 hour followed by 14 mg/kg per hour for 40 minutes) or administration of an equal volume of 5% dextrose in water. Each subject received the alternative treatment after an interval of at least 1 week. Blood methemoglobin concentrations were measured by multiwavelength co-oximetry at time 0, 15, 30, 50, 70, 90, 110, and 130 minutes. Area under the methemoglobin concentration-time curve (AUC) between 30 and 130 minutes was compared between groups using a 2-tailed, paired t test. RESULTS There were no statistically significant differences in the control and treatment groups with respect to baseline hemoglobin or methemoglobin concentrations, as well as nitrite-induced methemoglobin concentrations at the initiation of treatment (0.85+/-0.06 g/dL, 0.88+/-0.04 g/dL; mean+/-SEM; P =.31). Mean AUC for the control group (77.1+/-5.7 g x min/dL) was significantly lower than the mean AUC for the treatment group (84.5+/-4.7 g x min/dL); P =.01). CONCLUSION Intravenous NAC failed to enhance methemoglobin reduction in this model.

Hydroxocobalamin Versus Sodium Thiosulfate for the Treatment of Acute Cyanide Toxicity in a Swine (Sus scrofa) Model

STUDY OBJECTIVE We compare the efficacy of hydroxocobalamin to sodium thiosulfate to reverse the depressive effects on mean arterial pressure in a swine model of acute cyanide toxicity and gain a better understanding of the mechanism of action of the hydroxocobalamin in reversal of the toxicity. METHODS Swine were intubated, anesthetized, and instrumented with central arterial and venous lines and a pulmonary artery catheter. Animals (n=36) were randomly assigned to one of 3 groups: hydroxocobalamin alone (150 mg/kg), sodium thiosulfate alone (413 mg/kg), or hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 60 minutes after the start of antidotal infusion. Cyanide was infused until severe hypotension developed, defined as blood pressure 50% of baseline mean arterial pressure. Repeated-measures ANOVA was used to determine statistically significant changes between groups over time. RESULTS Time to hypotension (25, 28, and 33 minutes), cyanide dose at hypotension (4.7, 5.0, and 5.6 mg/kg), and mean cyanide blood levels (3.2, 3.7, and 3.8 μg/mL) and lactate levels (7, 8.2, 8.3 and mmol/L) were similar. All 12 animals in the sodium thiosulfate group died compared with 2 of 12 in the hydroxocobalamin/sodium thiosulfate group and 1 of 12 in hydroxocobalamin group. No statistically significant differences were detected between the hydroxocobalamin and hydroxocobalamin/sodium thiosulfate groups for carbon monoxide, mean arterial pressure, cyanide levels, or mortality at 60 minutes. Lactate level (2.6 versus 2.1 mmol/L), pH (7.44 versus 7.42), and bicarbonate level (25 versus 26 mEq/L) at 60 minutes were also similar between groups. CONCLUSION Sodium thiosulfate failed to reverse cyanide-induced shock in our swine model of severe cyanide toxicity. Further, sodium thiosulfate was not found to be effective when added to hydroxocobalamin in the treatment of cyanide-induced shock. Hydroxocobalamin alone was again found to be effective for severe cyanide toxicity.

Intravenous Cobinamide Versus Hydroxocobalamin for Acute Treatment of Severe Cyanide Poisoning in a Swine (Sus scrofa) Model

STUDY OBJECTIVE Hydroxocobalamin is a Food and Drug Administration-approved antidote for cyanide poisoning. Cobinamide is a potential antidote that contains 2 cyanide-binding sites. To our knowledge, no study has directly compared hydroxocobalamin with cobinamide in a severe, cyanide-toxic large-animal model. Our objective is to compare the time to return of spontaneous breathing in swine with acute cyanide-induced apnea treated with intravenous hydroxocobalamin, intravenous cobinamide, or saline solution (control). METHODS Thirty-three swine (45 to 55 kg) were intubated, anesthetized, and instrumented (continuous mean arterial pressure and cardiac output monitoring). Anesthesia was adjusted to allow spontaneous breathing with FiO2 of 21% during the experiment. Cyanide was continuously infused intravenously until apnea occurred and lasted for 1 minute (time zero). Animals were then randomly assigned to receive intravenous hydroxocobalamin (65 mg/kg), cobinamide (12.5 mg/kg), or saline solution and monitored for 60 minutes. A sample size of 11 animals per group was selected according to obtaining a power of 80%, an α of .05, and an SD of 0.17 in mean time to detect a 20% difference in time to spontaneous breathing. We assessed differences in time to death among groups, using Kaplan-Meier estimation methods, and compared serum lactate, blood pH, cardiac output, mean arterial pressure, respiratory rate, and minute ventilation time curves with repeated-measures ANOVA. RESULTS Baseline weights and vital signs were similar among groups. The time to apnea and cyanide dose required to achieve apnea were similar. At time zero, mean cyanide blood and lactate concentrations and reduction in mean arterial pressure from baseline were similar. In the saline solution group, 2 of 11 animals survived compared with 10 of 11 in the hydroxocobalamin and cobinamide groups (P<.001 between the 2 treated groups and the saline solution group). Time to return of spontaneous breathing after antidote was similar between hydroxocobalamin and cobinamide (1 minute 48 seconds versus 1 minute 49 seconds, respectively). Blood cyanide concentrations became undetectable at the end of the study in both antidote-treated groups, and no statistically significant differences were detected between the 2 groups for mean arterial pressure, cardiac output, respiratory rate, lactate, or pH. CONCLUSION Both hydroxocobalamin and cobinamide rescued severely cyanide-poisoned swine from apnea in the absence of assisted ventilation. The dose of cobinamide was one fifth that of hydroxocobalamin.

Vasopressin treatment of verapamil toxicity in the porcine model.

IntroductionVasopressin is a novel vasopressor agent used for intractable hypotension. There is little published data available on its use in the poisoned patient. We performed a randomized, controlled, blinded trial in a porcine model to study the effects of vasopressin infusion on mean arterial pressure after verapamil poisoning.MethodsEighteen anesthetized monitored swine received a verapamil infusion of 1 mg/kg/hr until the mean arterial pressure (MAP) had decreased to 70% of baseline. At this time, a continuous infusion of either vasopressin (0.01 U/kg/min) or an equal volume of normal saline was initiated. The swine were monitored for 60 minutes after initiation of the study infusion. The primary outcome was MAP.ResultsThere was no statistically significant difference between the two groups in MAP, cardiac output or systemic vascular resistance. One half (four of eight) of the animals in the vasopressin group died, compared with 20% (two of ten) of those in the saline group.ConclusionsVasopressin infusion decreased the survival of verapamil-poisoned swine when compared to those treated with saline alone in this experimental model.

Urinalysis is not reliable to detect a urinary tract infection in febrile infants presenting to the ED

OBJECTIVE Urinary tract infections are a common source of serious bacterial infections in febrile infants younger than 2 years. Our objective was to compare urinalysis with urine culture in the emergency department evaluation of febrile infants. METHODS A febrile infant registry was instituted at a tertiary care hospital treating an average of 55000 patients annually (27% children), from December 2002 to December 2003. Patients were eligible if they were younger than 3 months and had a temperature of at least 38 degrees C or if they were between 3 and 24 months of age and had a temperature of at least 39 degrees C. Data abstracted included age, sex, and temperature. Urinalysis (UA) and urine culture (UCx) results were obtained from electronic hospital archives. RESULTS Nine hundred eighty-five patients were entered into the febrile infant registry. Male patients comprised 55%. The mean age of patients was 12.6 months; median was 12 months. Four hundred thirty-five (78% of eligible patients) had both a UA and UCx from the same specimen, and there were 45 (10.3%) positive UCx result. Females accounted for 33 (73%) of 45 positive results. The sensitivity of UA for predicting a positive UCx result was 64% (95% confidence interval [CI], 49%-78%), whereas the specificity was 91% (95% CI, 88%-94%). The positive predictive value was 46% (95% CI, 31%-53%), with a negative predictive value of 96% (95% CI, 93%-97%). CONCLUSION Urinalysis is not reliable for the detection of urinary tract infections in febrile infants when compared with urine cultures.

Respiratory compromise in patients with rattlesnake envenomation

Respiratory compromise after rattlesnake envenomation (RSE) is an uncommon yet potentially lethal complication. We were interested in determining the frequency of respiratory compromise in patients treated for RSE. The incidence and indications for intubation were also determined. A retrospective chart review was conducted of all patients treated by medical toxicologists at a tertiary referral hospital between July, 1994 and November, 2000. Out of 294 total patients, 289 charts were reviewed. Of all 289 patients, 214 (74%) received Crotalidae Polyvalent Antivenin (Wyeth-Ayerst) and 23 (8%) had clinical evidence of respiratory compromise. Thirteen of 289 patients (4.4%) were intubated following RSE. No one was intubated for antivenin-induced complications. There were no deaths among studied patients during acute hospitalization. Respiratory compromise following RSE is rare, occurring in only 8% of studied patients. Only 2 patients (0.7%) required intubation as a direct consequence of RSE. No one required intubation for antivenin-induced hypersensitivity reactions.

Combined ingestion and subcutaneous injection of elemental mercury.

A 40-year-old man with a history of schizophrenia and inflammatory soft tissue lesions after self-injection of elemental mercury presented to the Emergency Department. Multiple skin abscesses associated with fever required operative debridement. An incidental finding of oral mercury ingestion was followed clinically and did not result in complications. Exposure to elemental mercury through injection or ingestion is an uncommon event, but one the Emergency Physician may encounter. Subcutaneous mercury injection should be managed with local wound debridement, whereas ingestions are rarely of clinical significance.